Investigations of potential gene-environment interactions may improve our understanding of the etiology of breast cancer, a disease where less than 30 to 40% of cases can be attributed to known risk factors. The objective of this proposal is to examine the influence of exogenous carcinogenic exposures (organochlorine compounds), a potential susceptibility factor (Glutathione S Transferase (GSTM1 genotype), and protective factors (antioxidants) on the risk of breast cancer. The proposed study will have a nested case-control design. Serum collected in 1974 (CLUE I cohort) and 1989 (CLUE II cohort) will be assayed for organochlorine compounds and antioxidant nutrients and GSTM1 genotyping will be done using the buffy coat collected in 1989. Results for the 341 persons who have developed breast cancer after donating blood will be compared with 341 matched controls. Independent and interactive effects of these factors on the risk of breast cancer will be examined. From the viewpoint of etiology, findings will aid in understanding the contribution of environmental organochlorine compound exposure to the development of breast cancer and the potential inherited susceptibility to the effects of these compounds. From the viewpoint of prevention, the modifying effects of antioxidants on the association between organochlorine compounds and breast cancer deserve particular attention since these are factors that are amenable to practical preventive measures.